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Dietary Calcium Alleviates Fluorine-Induced Liver Injury in Rats by Mitochondrial Apoptosis Pathway

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Abstract

Excessive fluoride (F) exposure can lead to liver damage; moreover, recent studies found that the addition of appropriate calcium (Ca) can alleviate the symptom of skeletal fluorosis. However, whether Ca can relieve F-induced liver damage through the mitochondrial apoptosis pathway has not been reported yet. Therefore, we assessed the liver morphology, serum transaminase content, liver oxidative stress-related enzymes, and apoptosis-related gene and protein expression in Sprague Dawley (SD) rats treated with 150 mg/L sodium fluoride (NaF) and different concentrations of calcium carbonate (CaCO3) for 120 days. Our results showed that NaF brought out pathological changes in liver morphology, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels increased, total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) content decreased, and malondialdehyde (MDA) content increased, suggesting that NaF caused hepatotoxicity and oxidative stress. In addition, the results of quantitative real-time PCR (qRT-PCR) and immunohistochemistry showed that NaF exposure upregulated the expression of Bcl-2-associated x protein (Bax), rho-related coiled-coil kinase 1 (ROCK1), cytochrome C (Cyto-C) mRNA and protein (P < 0.01), and downregulated B cell lymphoma 2 (Bcl-2) protein and mRNA (P < 0.01), indicating that excessive F exposure activated mitochondrial-mediated apoptosis in the liver. However, the addition of 1% CaCO3 to the diet significantly increased the expression of anti-apoptotic gene Bcl-2 (P < 0.01), inhibited the activation of the mitochondrial apoptosis pathway, and reduced mitochondrial damage. In summary, supplementing 1% CaCO3 in the diet can alleviate the NaF-induced liver cell damage through the mitochondrial apoptosis pathway.

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Data Availability

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgments

This research was supported by the China National Natural Science Foundation (Grant 31972751) and Shanxi Province Natural Science Foundation (Grant 201901D111230) and Shanxi Province Innovation Project for Graduate Students (Grant 2019SY219) and the Social Developmental Project of Jiangsu Province (BE2018715).

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Authors and Affiliations

  1. College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, Taigu, 030801, Shanxi, People’s Republic of China

    Haojie Li, Zijun Hao, Jiarong Yang, Yangfei Zhao & Jinming Wang

  2. Shanxi Key Laboratory of Environmental Veterinary Medicine, Shanxi Agricultural University, Jinzhong, Taigu, 030801, Shanxi, People’s Republic of China

    Haojie Li, Zijun Hao, Li Wang, Jiarong Yang, Yangfei Zhao & Jinming Wang

  3. Linjiang Sub-district Office, Tunliu District, Changzhi City, 046100, Shanxi Province, People’s Republic of China

    Li Wang

  4. Department of Basic Science, Shanxi Agricultural University, Jinzhong, Taigu, 030801, Shanxi, People’s Republic of China

    Xiaofang Cheng

  5. Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, 210014, Jiangsu, People’s Republic of China

    Haiyan Yuan

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  1. Haojie Li
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Li, H., Hao, Z., Wang, L. et al. Dietary Calcium Alleviates Fluorine-Induced Liver Injury in Rats by Mitochondrial Apoptosis Pathway. Biol Trace Elem Res 200, 271–280 (2022). https://doi.org/10.1007/s12011-021-02641-1

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